Diabetes, Vol 46, Issue 1 138-142, Copyright © 1997 by American Diabetes Association

ARTICLES

Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes

R Morishita, S Nakamura, Y Nakamura, M Aoki, A Moriguchi, I Kida, Y Yo, K Matsumoto, T Nakamura, J Higaki and T Ogihara
Department of Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Japan.

Endothelial cells are known to secrete various antiproliferative and vasodilating factors. Although injury of endothelial cells has been postulated as an initial trigger of the progression of atherosclerosis in patients with diabetes, the mechanisms of endothelial injury in diabetes are not yet clarified. Therefore, it is important to know the effects of high glucose on the factors that may influence endothelial cell growth. A novel member of endothelium-specific growth factors, hepatocyte growth factor (HGF), is produced in vascular cells. To investigate the effects of high glucose on vascular cells, we examined 1) the effects of high glucose on endothelial cell and vascular smooth muscle cell (VSMC) growth and 2) the effects of high glucose on local HGF production in endothelial cell and VSMC. Treatment of human aortic endothelial cell with a high concentration of D-glucose, but not mannitol and L-glucose, resulted in a significant decrease in cell number. Interestingly, addition of recombinant HGF attenuated high D-glucose-induced endothelial cell death. Therefore, we measured local HGF secretion of endothelial cell. Importantly, local HGF production was significantly decreased by high D-glucose treatment. In contrast, high D-glucose treatment resulted in a significant increase in the number of human aortic VSMCs, whereas local HGF production was significantly decreased in accordance with increase in D-glucose concentration. No significant changes in numbers were observed in VSMC treated with high mannitol and L-glucose. We also studied the mechanisms of local HGF suppression by high D-glucose. High D-glucose treatment stimulated transforming growth factor-beta (TGF-beta) concentration in endothelial cell and VSMC. Decreased local vascular HGF production was abolished by addition of anti-TGF-beta antibody. As TGF-beta inhibited local HGF production in endothelial cell and VSMC, increased TGF-beta induced by high D-glucose may suppress local HGF production. This study demonstrated that high D-glucose induced endothelial cell death, stimulated VSMC growth, and decreased local HGF production through the stimulation of TGF-beta production both in endothelial cell and VSMC. Overall, decrease in a local endothelial stimulant, HGF, by high D-glucose may be a trigger of endothelial injury in diabetes, potentially resulting in the progression of atherosclerosis.
CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Nakagami, N. Nakagawa, Y. Takeya, K. Kashiwagi, C. Ishida, S.-i. Hayashi, M. Aoki, K. Matsumoto, T. Nakamura, T. Ogihara, et al. Model of Vasculogenesis from Embryonic Stem Cells for Vascular Research and Regenerative Medicine Hypertension, July 1, 2006; 48(1): 112 - 119. [Abstract] [Full Text] [PDF]

				S. Yasuda, S. Miyazaki, M. Kanda, Y. Goto, M. Suzuki, Y. Harano, and H. Nonogi Intensive treatment of risk factors in patients with type-2 diabetes mellitus is associated with improvement of endothelial function coupled with a reduction in the levels of plasma asymmetric dimethylarginine and endogenous inhibitor of nitric oxide synthase Eur. Heart J., May 2, 2006; 27(10): 1159 - 1165. [Abstract] [Full Text] [PDF]

				W. Ito, A. Kanehiro, K. Matsumoto, A. Hirano, K. Ono, H. Maruyama, M. Kataoka, T. Nakamura, E. W. Gelfand, and M. Tanimoto Hepatocyte Growth Factor Attenuates Airway Hyperresponsiveness, Inflammation, and Remodeling Am. J. Respir. Cell Mol. Biol., April 1, 2005; 32(4): 268 - 280. [Abstract] [Full Text] [PDF]

				J. M. Cruzado, N. Lloberas, J. Torras, M. Riera, C. Fillat, I. Herrero-Fresneda, J. M. Aran, G. Alperovich, A. Vidal, and J. M. Grinyo Regression of Advanced Diabetic Nephropathy by Hepatocyte Growth Factor Gene Therapy in Rats Diabetes, April 1, 2004; 53(4): 1119 - 1127. [Abstract] [Full Text] [PDF]

				S. Mizuno and T. Nakamura Suppressions of chronic glomerular injuries and TGF-{beta}1 production by HGF in attenuation of murine diabetic nephropathy Am J Physiol Renal Physiol, January 1, 2004; 286(1): F134 - F143. [Abstract] [Full Text] [PDF]

				N. Komai, R. Morishita, S. Yamada, M. Oishi, S. Iguchi, M. Aoki, M. Sasaki, I. Sakurabayashi, J. Higaki, and T. Ogihara Mitogenic Activity of Oxidized Lipoprotein (a) on Human Vascular Smooth Muscle Cells Hypertension, September 1, 2002; 40(3): 310 - 314. [Abstract] [Full Text] [PDF]

				H. Nakagami, R. Morishita, K. Yamamoto, Y. Taniyama, M. Aoki, K. Yamasaki, K. Matsumoto, T. Nakamura, Y. Kaneda, and T. Ogihara Hepatocyte Growth Factor Prevents Endothelial Cell Death Through Inhibition of bax Translocation From Cytosol to Mitochondrial Membrane Diabetes, August 1, 2002; 51(8): 2604 - 2611. [Abstract] [Full Text] [PDF]

				Y. Taniyama, R. Morishita, K. Hiraoka, M. Aoki, H. Nakagami, K. Yamasaki, K. Matsumoto, T. Nakamura, Y. Kaneda, and T. Ogihara Therapeutic Angiogenesis Induced by Human Hepatocyte Growth Factor Gene in Rat Diabetic Hind Limb Ischemia Model: Molecular Mechanisms of Delayed Angiogenesis in Diabetes Circulation, November 6, 2001; 104(19): 2344 - 2350. [Abstract] [Full Text] [PDF]

				H. Nakagami, R. Morishita, K. Yamamoto, S.-i. Yoshimura, Y. Taniyama, M. Aoki, H. Matsubara, S. Kim, Y. Kaneda, and T. Ogihara Phosphorylation of p38 Mitogen-Activated Protein Kinase Downstream of Bax-Caspase-3 Pathway Leads to Cell Death Induced by High D-Glucose in Human Endothelial Cells Diabetes, June 1, 2001; 50(6): 1472 - 1481. [Abstract] [Full Text]

				K. Yamamoto, R. Morishita, S.-i. Hayashi, H. Matsushita, H. Nakagami, A. Moriguchi, K. Matsumoto, T. Nakamura, Y. Kaneda, and T. Ogihara Contribution of Bcl-2, but Not Bcl-xL and Bax, to Antiapoptotic Actions of Hepatocyte Growth Factor in Hypoxia-Conditioned Human Endothelial Cells Hypertension, May 1, 2001; 37(5): 1341 - 1348. [Abstract] [Full Text] [PDF]

				H. Nakagami, R. Morishita, K. Yamamoto, Y. Taniyama, M. Aoki, K. Matsumoto, T. Nakamura, Y. Kaneda, M. Horiuchi, and T. Ogihara Mitogenic and Antiapoptotic Actions of Hepatocyte Growth Factor Through ERK, STAT3, and Akt in Endothelial Cells Hypertension, February 1, 2001; 37(2): 581 - 586. [Abstract] [Full Text] [PDF]

				W. Liu, A. Schoenkerman, and W. L. Lowe Jr. Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells Am J Physiol Endocrinol Metab, October 1, 2000; 279(4): E782 - E790. [Abstract] [Full Text] [PDF]

				A. Cantón, R. Burgos, C. Hernández, C. Mateo, R. M Segura, J. Mesa, and R. Simó Hepatocyte growth factor in vitreous and serum from patients with proliferative diabetic retinopathy Br. J. Ophthalmol., July 1, 2000; 84(7): 732 - 735. [Abstract] [Full Text]

				Y Zhu, Y Hojo, U Ikeda, K Shimada;, and G F BAXTER Production of hepatocyte growth factor during acute myocardial infarction Heart, April 1, 2000; 83(4): 450 - 455. [Abstract] [Full Text]

				S. Shigematsu, K. Yamauchi, K. Nakajima, S. Iijima, T. Aizawa, and K. Hashizume D-Glucose and insulin stimulate migration and tubular formation of human endothelial cells in vitro Am J Physiol Endocrinol Metab, September 1, 1999; 277(3): E433 - E438. [Abstract] [Full Text] [PDF]

				K. Matsumoto, R. Morishita, A. Moriguchi, N. Tomita, Y. Yo, T. Nishii, K. Matsumoto, T. Nakamura, J. Higaki, and T. Ogihara Prevention of Renal Damage by Angiotensin II Blockade, Accompanied by Increased Renal Hepatocyte Growth Factor in Experimental Hypertensive Rats Hypertension, August 1, 1999; 34(2): 279 - 284. [Abstract] [Full Text] [PDF]

				E. Tsuchikane, A. Fukuhara, T. Kobayashi, M. Kirino, K. Yamasaki, T. Kobayashi, M. Izumi, S. Otsuji, H. Tateyama, M. Sakurai, et al. Impact of Cilostazol on Restenosis After Percutaneous Coronary Balloon Angioplasty Circulation, July 6, 1999; 100(1): 21 - 26. [Abstract] [Full Text] [PDF]

				K. Shinoda, S. Ishida, S. Kawashima, T. Wakabayashi, T. Matsuzaki, M. Takayama, K. Shinmura, and M. Yamada Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus Br. J. Ophthalmol., July 1, 1999; 83(7): 834 - 837. [Abstract] [Full Text]

				R. Morishita, S. Nakamura, S.-i. Hayashi, Y. Taniyama, A. Moriguchi, T. Nagano, M. Taiji, H. Noguchi, S. Takeshita, K. Matsumoto, et al. Therapeutic Angiogenesis Induced by Human Recombinant Hepatocyte Growth Factor in Rabbit Hind Limb Ischemia Model as Cytokine Supplement Therapy Hypertension, June 1, 1999; 33(6): 1379 - 1384. [Abstract] [Full Text] [PDF]

				R. Morishita, S. Yamada, K. Yamamoto, N. Tomita, I. Kida, I. Sakurabayashi, A. Kikuchi, Y. Kaneda, R. Lawn, J. Higaki, et al. Novel Therapeutic Strategy for Atherosclerosis : Ribozyme Oligonucleotides Against Apolipoprotein(a) Selectively Inhibit Apolipoprotein(a) But Not Plasminogen Gene Expression Circulation, November 3, 1998; 98(18): 1898 - 1904. [Abstract] [Full Text] [PDF]

				R. Morishita, S. Yamada, J. Higaki, N. Tomita, I. Kida, M. Aoki, A. Moriguchi, S.-i. Hayashi, I. Sakurabayashi, Y. Kaneda, et al. Conditioned Medium From HepG2 Cells Transfected With Human Apolipoprotein(a) Gene Stimulates Growth of Human Vascular Smooth Muscle Cells : Effects of Overexpression of Human Apolipoprotein(a) Gene Hypertension, August 1, 1998; 32(2): 215 - 222. [Abstract] [Full Text] [PDF]

				M. Nishimura, K. Nakano, M. Ushiyama, A. Nanbu, K. Ohtsuka, H. Takahashi, and M. Yoshimura Increased Serum Concentrations of Human Hepatocyte Growth Factor in Proliferative Diabetic Retinopathy J. Clin. Endocrinol. Metab., January 1, 1998; 83(1): 195 - 198. [Abstract] [Full Text]

				H. Matsushita, R. Morishita, I. Kida, M. Aoki, S.-i. Hayashi, N. Tomita, K. Yamamoto, A. Moriguchi, A. Noda, Y. Kaneda, et al. Inhibition of Growth of Human Vascular Smooth Muscle Cells by Overexpression of p21 Gene Through Induction of Apoptosis Hypertension, January 1, 1998; 31(1): 493 - 498. [Abstract] [Full Text] [PDF]

				N. Nakano, A. Moriguchi, R. Morishita, I. Kida, N. Tomita, K. Matsumoto, T. Nakamura, J. Higaki, and T. Ogihara Role of Angiotensin II in the Regulation of a Novel Vascular Modulator, Hepatocyte Growth Factor (HGF), in Experimental Hypertensive Rats Hypertension, December 1, 1997; 30(6): 1448 - 1454. [Abstract] [Full Text]

				Z. Zhang, K. Apse, J. Pang, and R. C. Stanton High Glucose Inhibits Glucose-6-phosphate Dehydrogenase via cAMP in Aortic Endothelial Cells J. Biol. Chem., December 15, 2000; 275(51): 40042 - 40047. [Abstract] [Full Text] [PDF]